Of decrements and disorders: assessing impairments in neurodevelopment in prospective studies of environmental toxicant exposures.

Prenatal and early life neurodevelopment is exquisitely sensitive to insult from environmental exposures. Identifying the effects of environmental toxicants on neurodevelopmental disorders is particularly important from a public health perspective because many of these exposures are modifiable and may be targeted for intervention. Studying these associations in prospective cohort studies that measure quantitative, dimensional traits related to neurodevelopmental disorders, using standardized instruments such as psychometric tests or rating scales, mitigates many of the challenges that arise when studying clinically diagnosed disorders. We consider validity and feasibility impacts resulting from this design approach, including: 1) enhanced prospective exposure assessment with high quality environmental measures during developmentally relevant windows; 2) reduced bias because studies of continuous outcomes do not recruit cases and controls and are therefore not vulnerable to control selection bias; 3) enhanced statistical power because traits are measured on all individuals in the cohort and power is not limited by the number of cases; 4) reduced outcome misclassification because measuring quantitative traits avoids lumping together individuals with very heterogeneous phenotypes into one category. We use autism spectrum disorders (ASD) as an example to illustrate the advantages of this approach. Investigating the determinants of neurodevelopmental disorders - particularly modifiable determinants such as environmental toxicant exposures - is of great public health importance, given the apparent substantial rise of disorders like ASD over the past few decades. The use of prospective designs measuring quantitative, dimensional traits offers a powerful opportunity to provide important clues to the etiology of these disorders and is likely to accelerate our understanding of the role of environmental toxicant exposures as risk factors.